A Busy Week for the EU Inspectorate Publishing Reports of GMP Non-Compliance

December 20, 2016

It’s been a busy week for newly published Eudra reports of GMP non-compliance. The inspections mentioned in the three reports posted this week were conducted in February and March of 2016. The first two clearly specify deficiencies in the area of data integrity. The three reports to these API and intermediate manufacturers provide yet another example how actions taken against a contract manufacturer can have potential impact on dozens of companies and their supply chain. Shortcomings in diligent auditing and oversight of CMO sites has both GMP implications and business and financial consequences. The three reports posted this week are addressed below:

The Sweden authorities report that Bend Research Inc. (Bend, OR) investigational products and commercial product are not manufactured in compliance with EU GMPs. The report of non-compliance was posted May 16, 2016 based on the outcome of the latest inspection on February 24, 2016. The operations in question are non-sterile API intermediates, packaging and quality control testing. The summary of non-compliance is reported as: “Repeated inspections with unacceptable level of GMP-compliance. Repeated failures to correct deficiencies and to provide requested and reliable information. During the last inspection (Feb 2016), 2 critical, 7 major and 12 other deficiencies were found. The two critical and one major deficiency concerns data integrity. Major deficiencies were also found in the areas of: Validation, Hygiene routines, Identification of mobile equipment in the multipurpose facilities, Documentation routines. Several findings from the two previous MPA inspections Aug-Sep 2015 and in Aug 2012 had not been corrected.” No pending Clinical Trials Application should be approved until a new GMP certificate is issued. No new EU marketing authorizations or line extension can be approved where the firm is the manufacturer until a new GMP certificate is issued. Actions recommended includes an interesting caveat: “These recommendations are not meant to interfere with the possibility of making exceptions for critical supply of a medically essential product (whether as a marketed product or as part of an ongoing clinical trial). If there is a significant patient risk connected to discontinuation of a treatment and no alternative treatment exists, the supply may be regarded as medically essential but this should be verified with the competent authority in the country concerned.”

The Italian authorities report that JP Laboratories Private Limited (India) is not compliant with EU GMPs for active substances. The inspection was conducted March 16, 2016. Twenty-eight (28) deficiencies were identified and nine of these were classified as major. These include: “Quality management – integrity and security of data in the quality system (1); – Personnel (2) – Building and facilities (1) – Materials management (1) – Production and In-Process control (1) – Laboratory control – integrity and security of analytical data (1); – Validation: equipment qualification (1) – Change control (1) The extent and severity of the findings, in combination with the repeated negative inspection outcome, demonstrates the inability of the company to sustain an acceptable GMP compliance level, and constitutes a critical risk for public health.” Although the observed deficiencies addressed only one product, the report states that the conclusions are to apply to all products manufactured at the site. The CEP is withdrawn and the competent authorities of the member states should evaluate the medical necessity of the products to determine whether supply should be limited or product recalls.

The Italian authorities determined that Krebs Biochemicals and Industries Limited,Plant Unit II(India) did not comply with EU GMPs. The inspection of this API manufacturer was conducted March 11, 2016. The product that was the subject of the inspection was the API for Simvastatin. Twenty-four (24)deficiencies were identified of which five were major and included the areas of “One in deviation management; One in personnel training; One in facilities; One in finished product storage management; One in production and monitoring of purified water.” Each competent authority is advised to determine the need for recalls. Prohibition of supply is recommended unless there are no viable alternatives for medically necessary products. The supplier should not be approved for any new applications. Finally, “Assessment of the findings of the EDQM inspection is currently on going: all CEP’s suspension recommended by the inspection team was officially endorsed by the Ad Hoc Committee on 30 March 2016.”

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